Active peptides derived from angiotensin II

It has been recently shown that angiotensin II (Ang II) is not the only act ive peptide of the renin-angiotensin system. Several of its degradation pro ducts including Ang III (obtained by deletion of the N terminal amino acids ), Ang IV (obtained by deletion of the two N terminal amino acids), and Ang II (1-7) (obtained by deletion of the C terminal amino acid), also possess biological functions. These peptides are formed via the activity of severa l enzymes: angiotensin - converting enzyme, aminopeptidases A and N, neutra l endopeptidase and prolylendopeptidase. Ang ill pos sesses most of the pro perties of Ang II and shares the same receptors AT(1) and AT(2). In additio n this peptide is particularly important in brain physiology and plays a ma jor role in the secretion of arginine vasopressine. Ang IV possesses its ow n recepton distinct from AT(1) and AT(2). Some of its effects (for example, stimulation of the synthesis of the type 1 inhibitor of plasminogen activa tor by endothelial cells) were previously attributed to Ang II. Others effe cts, like renal and cerebral vasodilatation, are opposed to Ang II effects. The role of Ang IV in renal physiology remains to be determined. Ang II (1 -7() exhibits direct and indirect effects, the latter resulting from Ang Il (1-7)- dependent formation of nitric oxide and vasodilatory prostaglandins . Ang II 1-7) potentiates the hypotensive effect of bradykinin and plays al so a major role in the control of the hydroelectrolytic balance. It pos ses ses its own receptor: AT(1.7), recognizable by (sar(1)-thr(8)) Ang II or Sa rthran. Finally Ang II (1-7) is converted into Ango II (1-5), by angiotensi n-converting enzyme. This peptide is inactive. All of these enzymes, peptid es and receptors are present in kidney. Thus the renin-angiotensin system a ppears to be much more complicated than thought a few years ago, setting th e problem of new therapeutic tools for the treatment of hypertension and gl omerulosclerosis.